A field-portable instrument that can determine blood levels of specific toxic metals is vital in establishing the link between toxic exposure, induced mutation, and genetic expression. In addition, screening of vulnerable populations for toxic metal exposure is critical to permit timely medical intervention to mitigate physiological damage. Such measurements are therefore important for both clinical and epidemiological applications. Standard assay methods require trained personnel to obtain samples to be sent to off-site laboratories, increasing costs and handling errors, and imposing a delay in identifying exposure sources. The overall goal of the proposed work will be to develop a small, easy-to-use, hand-held instrument used with disposable silicon microchips to provide rapid, in-field simultaneous detection of lead, cadmium, and zinc in a single sub-microliter blood sample. The microsampling and assay chip integrates a microneedle comparable in size to a human hair for painless blood sampling with a microcuvette containing an electrochemical detection structure. The biochip can be cost- effectively fabricated using MEMS (microelectromechanical systems) technology. The assay will employ electrochemical-stripping analysis;a proven technique for an accurate and precise detection of trace quantities of toxic heavy metals without requiring sample de-oxygenation. The instrument is ideal for field use, and can be used by untrained personnel. Phase I demonstrated feasibility by: developing the assay and validating it with in vitro testing, designing the microchip and fabricating key components, and developing components of the measurement and control instrumentation. In Phase II, a complete prototype system will be fabricated and evaluated. This system will consist of a hand-held instrument that will be used in conjunction with a single-use consumable. Both in vitro testing and in vivo testing in animal models will validate performance of the prototype system. PUBLIC HEALTH RELEVANCE: Successful completion of this work will lead to the development of a small, easy-to-use, hand- held instrument to provide rapid, in-field simultaneous detection of lead, cadmium and zinc in blood, using a miniature electrochemical-stripping assay in a silicon microchip disposable. The ability to provide rapid in-field or point-of-care data will substantially improve treatment of overexposure to toxic agents, and improve public health. Furthermore, examining the global effects of toxic metals on gene expression will help researchers determine patterns of biological response, and discover the underlying mechanisms of toxicity.